Effect of beta-blockade and ACE inhibition on B-type natriuretic peptides in stable patients with systolic heart failure

Cardiovasc Drugs Ther. 2008 Aug;22(4):305-11. doi: 10.1007/s10557-008-6099-6. Epub 2008 Feb 29.

Abstract

Introduction: The long-term effect of beta-blockade on the plasma levels of natriuretic peptides BNP and its N-terminal counterpart, NT-proBNP, as risk markers in heart failure (HF) is obscure.

Methods: Stable systolic HF patients from the CARMEN study were divided in groups matching their randomised treatment allocation: Carvedilol, enalapril or carvedilol+enalapril. Changes in BNP and NT-proBNP from baseline to 6 months maintenance visit were evaluated in each treatment arm. Furthermore, the prognostic value of BNP and NT-proBNP during monotherapy with carvedilol was assessed with univariate Cox proportional hazards models using a combined endpoint of all cause mortality and cardiovascular hospitalisation.

Results: NT-proBNP and BNP were significantly reduced after six months treatment with enalapril (NT-proBNP 1,303 to 857 pg/ml (P < 0.001), BNP 119 to 85 pg/ml (P < 0.001)) or carvedilol+enalapril (NT-proBNP 1,223 to 953 pg/ml (P = 0.003), BNP 117 to 93 pg/ml (P = 0.01)). In contrast, no change was observed in the carvedilol group (NT-proBNP 907 to 1,082 pg/ml (P = 0.06), BNP 114 to 130 pg/ml (P = 0.15). The prognostic value of NT-proBNP and BNP was maintained in the carvedilol group (NT-proBNP HR 1.018 95% CI (1.005-1.032), BNP 1.171 (1.088-1.260)).

Conclusion: Treatment of HF patients with carvedilol alone does not reduce levels of natriuretic peptides, but treatment with enalapril does. Both BNP and NT-proBNP predict death and hospitalisation in HF patients treated with carvedilol for six months. The clinical implication of our results is that NT-proBNP and BNP can be used as risk markers of death and cardiovascular hospitalisations in systolic HF patients receiving carvedilol without ACE inhibition.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biomarkers / blood
  • Carbazoles / therapeutic use*
  • Carvedilol
  • Chronic Disease
  • Double-Blind Method
  • Drug Therapy, Combination
  • Enalapril / therapeutic use*
  • Europe
  • Female
  • Heart Failure, Systolic / drug therapy*
  • Heart Failure, Systolic / metabolism
  • Heart Failure, Systolic / mortality
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood
  • Propanolamines / therapeutic use*
  • Proportional Hazards Models
  • Risk Assessment
  • Time Factors
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Carbazoles
  • Peptide Fragments
  • Propanolamines
  • pro-brain natriuretic peptide (1-76)
  • Carvedilol
  • Natriuretic Peptide, Brain
  • Enalapril